IL-33 in Mental Disorders

Abstract

Mental disorders are common in the general population; every year about 25% of the total European population is affected by a mental condition. The prevalence of psychiatric disorders might be underestimated. Emerging evidence highlights the role of immune response as a key factor in MDs. Immunological biomarkers seem to be related to illness progression and to treatment effectiveness; several studies suggest strong associations among IL-6, TNFa, S100b, IL 1b, and PCR with affective or schizophrenic disorders. The purpose of this review is to examine and to understand the possible link between mental disorders and interleukin 33 to clarify the role of this axis in the immune system. We found 13 research papers that evaluated interleukin 33 or interleukin 31 levels in subjects affected by mental disorders. Eight studies investigated cytokines in affective disorders. Three studies measured levels of IL-33 in schizophrenia and two studies focused on patients affected by autism spectrum disorders. Alterations in brain structure and neurodevelopmental outcome are affected by multiple levels of organization. Disorders of the autoimmune response, and of the IL-33/31 axis, may therefore be one of the factors involved in this process. These results support the evidence that alarmins, particularly the IL-33/31 axis, need more consideration among researchers and practitioners.

Breast cancer in schizophrenia could be interleukin-33-mediated

“…For example, Miao et al [ 59 ] in 2021 highlighted that increased IL-33 levels might reduce brain damage in patients with intracerebral hemorrhage. The reviewed results support the evidence of elevated IL-33 serum levels in the acutisation of schizophrenia and depression, suggesting the involvement of this axis in the processes of relapse and recurrence of mental disorder[ 37 ].…”

“…The role of DAMPs in neurodegenerative diseases has already been recognized in sterile inflammation. As recently summarized by Pandolfo et al [ 37 ], acute or chronic stress may trigger sterile inflammation associated with DAMPs and may be an etiopathogenetic mechanism for affective disorders.…”

Interrelationship and Sequencing of Interleukins4, 13, 31, and 33 – An Integrated Systematic Review: Dermatological and Multidisciplinary Perspectives

“…The authors suggest that when a stressor arises in an individual with genetic susceptibility, an abnormal increase in IL-33 occurs and determines acute symptoms in schizophrenia and affective disorders, as well as the appearance of a new recurrence in major depression disorder. 190 In patients with schizophrenia, IL-33 and ST2 levels have been positively correlated with cognitive performance, but there was difference in the levels of each molecule between patients and healthy controls. Genetic studies have revealed that specific IL-33 polymorphisms can determine a decreased risk of susceptibility to developing schizophrenia, as well as an increased risk of developing major depressive disorder.…”

Schizophrenia and Alarmins

“…Upon release, IL-33 binds to its receptor complex comprising ST2 and IL-1RAcP (IL-1 receptor accessory protein) to activate the nuclear factor-κB and mitogen-activated protein kinase pathways, thereby driving multiple biological processes [53,54]. ST2 receptor is expressed on mast cells and other immune cells, including dendritic cells, monocytes, granulocytes, and Th2 lymphocytes [10,11]. IL-33 and its receptor ST2 participate in the interaction between immune cells and play an important role in diseases of the central nervous system.…”

“…Most importantly, Alarmins can both recruit and activate antigen-presenting cells, enhancing the adaptive immune response and serving as early warning signals to activate the innate and adaptive immune systems [8,10]. However, the excessive release of alarmins after cell damage can massively amplify the immune response and cause further damage in a proinflammatory loop [11].…”